The major aim of this study is to examine laboratory measures of pain sensitivity, cerebral spinal fluid (CSF) levels of substance P, and brain regional cerebral blood flow (rCBF) in 3 groups of subjects. These groups are (a) rheumatology clinic patients with fibromyalgia; (b) community residents with fibromyalgia who have not consulted a physician about their painful symptoms; and (c) healthy controls. Most of our findings have been consistent with our hypotheses. That is, both the patients and community residents with fibromyalgia differ from health controls in pain sensitivity, CSF levels of substance P, and in resting state levels of brain rCBF. Moreover, there are few differences between patients and community residents with fibromyalgia on these variables despite the fact that patients show significantly higher levels of psychological distress. Thus, differences in pain sensitivity and pain-related physiologic variables between persons with fibromyalgia and healthy individuals are not due primarily to psychological distress.